Possible Role of Meckel's Scan Fused with SPECT CT Imaging: Unraveling the Cause of Abdominal Pain and Obscure-Overt Gastrointestinal Bleeding

A 27-year-old male presented with recurrent abdominal pain and high volume hematochezia despite undergoing extensive testing and a right hemicolectomy 3 years prior for a linear bleeding ulceration in the ascending colon. Studies at the University of Michigan included esophagogastroduodenoscopy (EGD), colonoscopy and video capsule endoscopy (VCE), revealing an arteriovenous malformation (AVM) in the terminal ileum. He was hospitalized for recurrent symptoms. His presentation suggested a small bowel source of obscure-overt GI bleeding based on prior non-diagnostic colonoscopy and EGD and a bilious nasogastric lavage. Tagged red blood cell scan localized bleeding to the right lower quadrant. Colonoscopy showed fresh blood in the terminal ileum without a clear source. Angiography showed no evidence of bleeding or terminal ileal AVM. A novel Meckel's scan fused with SPECT imaging showed focal uptake in the terminal ileum. The patient underwent Meckel's diverticulectomy with sparing of adjacent bowel and has remained asymptomatic for 19 months. This case illustrates that patients with obscure-overt GI bleeding require a step-wise multi-modality diagnostic work-up. Because Meckel's scans are false-positive in 28% of adults, Meckel's scan fused with SPECT imaging may offer an approach to refine diagnostic accuracy of either scan alone, but requires further investigation. Exploratory laparotomy should be reserved as a last option and is best performed with intraoperative endoscopy

Modified granular impact force laws for the OSIRIS-REx touchdown on the surface of asteroid (101955) Bennu

The OSIRIS-REx mission collected a sample from the surface of the asteroid (101955) Bennu in October 2020. Here we study the impact of the OSIRIS-REx Touch-and-Go Sampling Acquisition Mechanism (TAGSAM) interacting with the surface of an asteroid in the framework of granular physics. Traditional approaches to estimating the penetration depth of a projectile into a granular medium include force laws and scaling relationships formulated from laboratory experiments in terrestrial-gravity conditions. However, it is unclear that these formulations extend to the OSIRIS-REx scenario of a 1300-kg spacecraft interacting with regolith in a microgravity environment. We studied the TAGSAM interaction with Bennu through numerical simulations using two collisional codes, pkdgrav and GDC-i. We validated their accuracy by reproducing the results of laboratory impact experiments in terrestrial gravity. We then performed TAGSAM penetration simulations varying the following geotechnical properties of the regolith: packing fraction (P), bulk density, inter-particle cohesion (σc), and angle of friction (ϕ). We find that the outcome of a spacecraft-regolith impact has a non-linear dependence on packing fraction. Closely packed regolith (P≳0.6) can effectively resist the penetration of TAGSAM if ϕ≳28° and/or σc≳50 Pa. For loosely packed regolith (P≲0.5), the penetration depth is governed by a drag force that scales with impact velocity to the 4/3 power, consistent with energy conservation. We discuss the importance of low-speed impact studies for predicting and interpreting spacecraft-surface interactions. We show that these low-energy events also provide a framework for interpreting the burial depths of large boulders in asteroidal regolith

Global geologic map of asteroid (101955) Bennu indicates heterogeneous resurfacing in the past 500,000 years

Global geologic maps are useful tools for efficient interpretation of a planetary body, and they provide global context for the diversity and evolution of the surface. We used data acquired by the OSIRIS-REx spacecraft to create the first global geologic map of the near-Earth asteroid (101955) Bennu. As this is the first geologic map of a small, non-spherical, rubble-pile asteroid, we discuss the distinctive mapping challenges and best practices that may be useful for future exploration of similar asteroids, such as those to be visited with the Hera and Janus missions. By mapping on two centimeter-scale global image mosaics (2D projected space) and a centimeter-scale global shape model (3D space), we generated three input maps respectively describing Bennu's shape features, geologic features, and surface texture. Based on these input maps, we defined two geologic units: the Smooth Unit and the Rugged Unit. The units are differentiated primarily on the basis of surface texture, concentrations of boulders, and the distributions of lineaments, mass movement features, and craters. They are bounded by several scarps. The Rugged Unit contains abundant boulders and signs of recent mass movement. It also has fewer small (<20 m), putatively fresh craters than the Smooth Unit, suggesting that such craters have been erased in the former. Based on these geologic indicators, we infer that the Rugged Unit has the younger surface of the two. Differential crater size-frequency distributions and the distribution of the freshest craters suggest that both unit surfaces formed ~10–65 million years ago, when Bennu was located in the Main Asteroid Belt, and the Smooth Unit has not been significantly resurfaced in the past 2 million years. Meanwhile, the Rugged Unit has experienced resurfacing within the past ~500,000 years during Bennu's lifetime as a near-Earth asteroid. The geologic units are consistent with global diversity in slope, surface roughness, normal albedo, and thermal emission spectral characteristics. The site on Bennu where the OSIRIS-REx mission collected a regolith sample is located in the Smooth Unit, in a small crater nested within a larger one. So although the Smooth Unit is an older surface than the Rugged Unit, the impact-crater setting indicates that the material sampled was recently exposed. Several similarities are apparent between Bennu and asteroid (162173) Ryugu from a global geologic perspective, including two geologic units distinguishable by variations in the number density of boulders, as well as in other datasets such as brightness

Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Altres ajuts: Max Planck Society (Germany).The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Method of estimating maximum VOC concentration in void volume of vented waste drums using limited sampling data: Application in transuranic waste drums

A test program has been conducted at the Idaho National Engineering Laboratory to demonstrate that the concentration of volatile organic compounds (VOCs) within the innermost layer of confinement in a vented waste drum can be estimated using a model incorporating diffusion and permeation transport principles as well as limited waste drum sampling data. The model consists of a series of material balance equations describing steady-state VOC transport from each distinct void volume in the drum. The primary model input is the measured drum headspace VOC concentration. Model parameters are determined or estimated based on available process knowledge. The model effectiveness in estimating VOC concentration in the headspace of the innermost layer of confinement was examined for vented waste drums containing different waste types and configurations. This paper summarizes the experimental measurements and model predictions in vented transuranic waste drums containing solidified sludges and solid waste